Using an established human RPE cell line (ARPE-19), we characterized the complement inhibiting-properties of PTX3 in physiological and inflammatory AMD-like (i.e., in the presence of TNF-α or IL-1β) conditions, and proposed a novel mechanism of complement regulation by this pentraxin with potential implications in the pathogenesis of AMD. This evidence concerns the gene TNF and age-related macular degeneration.